During liver regeneration, quiescent hepatocytes reenter the cell cycle, proliferate and repopulate the diseased liver. This process is observed in many forms of acute liver injury specifically those caused by viruses, toxins and trauma. Therefore, prognosis in acute liver failure often depends on the ability of proliferation to outlast liver cell necrosis. The long-term objective of the studies outlined here is to use recent knowledge of events that regulate exit from quiescence to identify liver specific targets in the initiation of liver regeneration. The first aim of the study is to evaluate for novel cyclin dependent kinase activities that regulate the transition from quiescence to active cell cycling. We believe that cyclin dependent kinase activities that precede the canonical Gi cyclins are important in transiting from G0 to GI during the regenerative process. The second aim of the study is to design a siRNA based screen that targets genes up regulated in the priming phase of liver regeneration. The goal is to identify genes whose products are necessary for cycle progression. Our hope is to identify physiologically relevant molecules that can be therapeutic targets for enhancement of liver proliferation. A cell based assay using H35 rat liver cell line, which can undergo the transition from quiescence to cell cycle reentry, will be used for both lines of inquiry. [unreadable] [unreadable] [unreadable]